Team of scientists unveil new features on how bacteria immunity function

The CRISPR-Cas systems protect bacteria from viruses and plasmids

MOSCOW, March 6. /TASS/ Researchers from Russia and the US supervised by the Chief of Skoltech Center for Data-Intensive Biomedicine and Biotechnology Professor Konstantin Severinov have uncovered new specific properties of the immune system of bacteria, CRISPR-Cas, which might assist in epidemiology studies, Skoltech’s press office reported. The study’s results have been published in journal Nucleic Acids Research.

"The results of our research might be helpful in creating new bacterial strains and for epidemiologic studies," Olga Murashova, Skoltech PhD student and one of the study’s co-authors said.

The CRISPR-Cas systems protect bacteria from viruses and plasmids. In CRISPR-Cas systems, there are segments of DNA of bacteria, the "CRISPR-cassettes" and the genes of Cas proteins which ensure the functioning of the system. In the CRISPR-cassette, replicas of segments of virus genes - spacers - a kind of mask from the alien genes, are stored. If the spacer’s sequence matches the sequence of alien DNA that had appeared in the cell, the Cas proteins would recognize and cut it.

An article penned by Skoltech PhD student Alexandra Strotskaya and her colleagues is devoted to the study of the process of bacteria infected with bacteriophages (viruses of bacteria) containing the spacers corresponding to these viruses. In some cases, namely if bacteria are exposed to the attack of lytic phages T5 and T7, which create many replicas inside the cell until the bacteria die, nearly all bacteria die.

"The most important and most unexpected conclusion from our work is that in contrast to the "normal" immune systems, e.g. the human one, the CRISPR-Cas system does not save individual cells: all cells infected by lytic phages essentially die.

However, as opposed to usual infections of unprotected cells, in cells with CRISPR-Cas, the virus offspring is suppressed. In other words, the infected cells capable of recognizing virus DNA by means of CRISPR-Cas die altruistically to save other cell and to decrease the probability of infection propagation through the population, " Strotskaya explained.

The article by Skoltech PhD student Olga Murashova is about how the spacer corresponding to the alien DNA, gets into the CRISPR-cassette. Incorporating spacers occurs while the infected cells are trying to cope with a virus by cutting its DNA. According to the study made by another research group at Skoltech, if an alien gene is cut, it does not guarantee its deactivation. In some cases, all the bacteria attacked by a virus, die although they have a corresponding spacer.

Murashova and her colleagues have tracked the protection mechanics during which the Cas protein in several steps cut an almost entire alien sequence making a great variety of spacers from it. These new spacers incorporate into CRISPR-cassette allowing the cell and its offshoots the possibility to fight the virus more effectively. Previously, this mechanism had been never studied (in vivo) on living bacteria, and a complete picture of the process has not been obtained. "Our results have provided the data to build the whole model of CRISPR-immunity starting from the initial "vaccination", that is from acquiring a new spacer to the destruction of a viral DNA in the course of subsequent infections," Murashova elaborated.